The total proteolytic activity in lymph node and thymus lymphocytes of rats with acute EAE probably consists of at least two enzymes. One of these is relatively easily extracted, and hydrolyzes myelin basic protein and polylysine. The distribution is like that of lysosomal enzymes. The other enzyme activity appears to be very strongly membrane bound. These enzymes will be extracted using strong salt, freezing, and thawing procedures, and mild detergents, and attempts will be made to purify these sufficiently to separate them and to determine their nature. A comparison of the direct effects of activated macrophages and lymphocytes from rats on CNS and PNS myelin will be made. Macrophages will be enriched from the peritoneal cavity and lymphocytes prepared from lymph nodes of rats in acute stages of experimental allergic encephalomyelitis and experimental allergic neuritis. These cells will be incubated with purified CNS and PNS myelin and the myelin proteins studied by polycrylamide gel electrophoresis for evidence of breakdown. Altough it is suspected that basic protein is most vulnerable in CNS myelin, the first point of attack on PNS myelin is unknown. Results of these studies may provide insight as to the nature and mechanism of myelin breakdown in demyelinating diseases.